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Effects of Vitamin D Receptor, Metallothionein 1A, and 2A Gene Polymorphisms on Toxicity of the Peripheral Nervous System in Chronically Lead-Exposed Workers.

ABSTRACT: Chronic exposure to lead is neurotoxic to the human peripheral sensory system. Variant vitamin D receptor (VDR) genes and polymorphisms of metallothioneins (MTs) are associated with different outcomes following lead toxicity. However, no evidence of a relationship between lead neurotoxicity and polymorphisms has previously been presented. In this study, we investigated the relationship between the polymorphisms of VDR, MT1A, and MT2A genes and lead toxicity following chronic occupational lead exposure. We measured vibration perception thresholds (VPT) and current perception thresholds (CPT) in 181 workers annually for five years. The outcome variables were correlated to the subject's index of long-term lead exposure. Polymorphisms of VDR, MT1A, and MT2A were defined. The potential confounders, including age, sex, height, smoking, alcohol consumption, and working life span, were also collected and analyzed using linear regression. The regression coefficients of some gene polymorphisms were at least 20 times larger than regression coefficients of time-weighted index of cumulative blood lead (TWICL) measures. All regression coefficients of TWICL increased slightly. MT1A rs11640851 (AA/CC) was associated with a statistically significant difference in all neurological outcomes except hand and foot VPT. MT1A rs8052394 was associated with statistically significant differences in hand and foot CPT 2000 Hz. In MT2A rs10636, those with the C allele showed a greater effect on hand CPT than those with the G allele. Among the VDR gene polymorphisms, the Apa rs7975232 (CC/AA) single nucleotide polymorphism was associated with the greatest difference in hand CPT. MT2A rs28366003 appeared to have a neural protective effect, whereas Apa (rs7975232) of VDR and MT2A rs10636 increased the neurotoxicity as measured by CPT in the hands. MT1A rs8052394 had a protective effect on large myelinated nerves. MT1A rs11640851 was associated with susceptibility to neurotoxicity.

SUBMITTER: Liu HL

PROVIDER: S-EPMC7215364 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Effects of Vitamin D Receptor, Metallothionein 1A, and 2A Gene Polymorphisms on Toxicity of the Peripheral Nervous System in Chronically Lead-Exposed Workers.

Liu Hsin-Liang HL Chuang Hung-Yi HY Hsu Chien-Ning CN Lee Su-Shin SS Yang Chen-Cheng CC Liu Kuan-Ting KT

International journal of environmental research and public health 20200423 8

Chronic exposure to lead is neurotoxic to the human peripheral sensory system. Variant vitamin D receptor (VDR) genes and polymorphisms of metallothioneins (MTs) are associated with different outcomes following lead toxicity. However, no evidence of a relationship between lead neurotoxicity and polymorphisms has previously been presented. In this study, we investigated the relationship between the polymorphisms of VDR, MT1A, and MT2A genes and lead toxicity following ...[more]

PMID: 32340109

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Project description:BackgroundExposure to lead (Pb) has been associated with endocrine, hematological, gastrointestinal, renal and neurological problems in humans. However, effects on the thyroid gland are controversial.ObjectivesThe aim of the present study was to assess thyroid function in foundry workers occupationally exposed to Pb and the mechanism of oxidative-antioxidant imbalance.MethodsThyroid function parameters and markers of oxidative stress were examined in 59 adult males who had been occupationally exposed to Pb. The results were then compared to those of 28 male subjects who had no history of Pb exposure or thyroid abnormalities and served as a control group.ResultsMean blood lead levels (16.5±1.74 μg/dl) were significantly higher among the exposed workers compared to those of the control group (12.8±1.16 μg/dl, (p <0.001)). The exposed group had significantly increased free triiodothyronine (FT3), free thyroxine (FT4) and significantly decreased thyroid stimulating hormone (TSH) (1.77±0.44 μIU/ml), whereas the control group had a TSH level of 2.61±0.94 μIU/ml (p< 0.0001). A state of oxidative stress was indicated by the significant increase in mean levels of malondialdehyde (MDA) and significant decrease in glutathione (GSH) (p < 0.0001). There was a significant positive correlation (r=0.358, p <0.05) between blood lead levels (BLL) and duration of employment, while BLL showed a significant negative correlation with TSH (r =-0.486, p <0.001), and GSH (r =-0.336, p <0.05). Of the occupationally exposed workers, 32.76% had elevated thyroid hormones. The results showed a significant positive relationship between GSH and TSH (β coefficient=0.274, p < 0.05), MDA with FT3 (β coefficient=0.355, p < 0.05) and FT4 (β coefficient = 0.491, p < 0.0001) among exposed workers.ConclusionsWorkers exposed to Pb dust proved to be at risk for hyperthyroidism, which was found to have a significant role in oxidative-antioxidant imbalance present among workers with increasing duration of exposure.Participant consentObtained.Ethics approvalThis study was approved by the Ethical Committee of the National Research Centre in Egypt (NRC) under the registration number 15225.Competing interestsThe authors declare no competing financial interests.

Dataset Information

Effects of Vitamin D Receptor, Metallothionein 1A, and 2A Gene Polymorphisms on Toxicity of the Peripheral Nervous System in Chronically Lead-Exposed Workers.

Publications

Effects of Vitamin D Receptor, Metallothionein 1A, and 2A Gene Polymorphisms on Toxicity of the Peripheral Nervous System in Chronically Lead-Exposed Workers.

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